FOXM1 expression in rhabdomyosarcoma: a novel prognostic factor and therapeutic target

Masaaki Kuda, Kenichi Kouhashi, Yuichi Yamada, Akira Maekawa, Yoshiaki Kinoshita, Tetsuya Nakatsura, Yukihide Iwamoto, Tomoaki Taguchi, Yoshinao Oda

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The transcription factor Forkhead box M1 (FOXM1) is known to play critical roles in the development and progression of various types of cancer, but the clinical significance of FOXM1 expression in rhabdomyosarcoma (RMS) is unknown. This study aimed to determine the role of FOXM1 in RMS. We investigated the expression levels of FOXM1 and vascular endothelial growth factor (VEGF) and angiogenesis in a large series of RMS clinical cases using immunohistochemistry (n = 92), and we performed clinicopathologic and prognostic analyses. In vitro studies were conducted to examine the effect of FOXM1 knock-down on VEGF expression, cell proliferation, migration, and invasion in embryonal RMS (ERMS) and alveolar RMS (ARMS) cell lines, using small interference RNA (siRNA). High FOXM1 expression was significantly increased in the cases of ARMS, which has an adverse prognosis compared to ERMS (p = 0.0310). The ERMS patients with high FOXM1 expression (n = 25) had a significantly shorter survival than those with low FOXM1 expression (n = 24; p = 0.0310). FOXM1 expression was statistically correlated with VEGF expression in ERMS at the protein level as shown by immunohistochemistry and at the mRNA level by RT-PCR. The in vitro study demonstrated that VEGF mRNA levels were decreased in the FOXM1 siRNA-transfected ERMS and ARMS cells. FOXM1 knock-down resulted in a significant decrease of cell proliferation and migration in all four RMS cell lines and invasion in three of the four cell lines. Our results indicate that FOXM1 overexpression may be a prognostic factor of RMS and that FOXM1 may be a promising therapeutic target for the inhibition of RMS progression.

Original languageEnglish
Pages (from-to)5213-5223
Number of pages11
JournalTumor Biology
Volume37
Issue number4
DOIs
Publication statusPublished - Apr 1 2016

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Rhabdomyosarcoma
Vascular Endothelial Growth Factor A
Alveolar Epithelial Cells
RNA Interference
Cell Line
Cell Movement
Therapeutics
Immunohistochemistry
Alveolar Rhabdomyosarcoma
Cell Proliferation
Embryonal Rhabdomyosarcoma
Forkhead Transcription Factors
Messenger RNA
Polymerase Chain Reaction
Survival
Neoplasms
Proteins

All Science Journal Classification (ASJC) codes

  • Cancer Research

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FOXM1 expression in rhabdomyosarcoma : a novel prognostic factor and therapeutic target. / Kuda, Masaaki; Kouhashi, Kenichi; Yamada, Yuichi; Maekawa, Akira; Kinoshita, Yoshiaki; Nakatsura, Tetsuya; Iwamoto, Yukihide; Taguchi, Tomoaki; Oda, Yoshinao.

In: Tumor Biology, Vol. 37, No. 4, 01.04.2016, p. 5213-5223.

Research output: Contribution to journalArticle

Kuda, Masaaki ; Kouhashi, Kenichi ; Yamada, Yuichi ; Maekawa, Akira ; Kinoshita, Yoshiaki ; Nakatsura, Tetsuya ; Iwamoto, Yukihide ; Taguchi, Tomoaki ; Oda, Yoshinao. / FOXM1 expression in rhabdomyosarcoma : a novel prognostic factor and therapeutic target. In: Tumor Biology. 2016 ; Vol. 37, No. 4. pp. 5213-5223.
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